amphotericin-b and indole

In connection with our research program on the development of novel anti-tubercular candidates, herein we report the design and synthesis of two different sets of indole-thiazolidinone conjugates (8a,b; 11a-d) and (14a-k; 15a-h). The target compounds were evaluated for their in vitro antibacterial and antifungal activities against selected human pathogens viz. Staphylococcus aureus (Gram positiveve), Pseudomonas aeruginosa, Escherichia coli (Gram negative), Mycobacterium tuberculosis (Acid-fast bacteria), Aspergillus fumigates and Candida albicans (fungi). Moreover, eukaryotic cell-toxicity was tested via an integrated ex vivo drug screening model in order to evaluate the selective therapeutic index (SI) towards antimicrobial activity when microbes are growing inside primary immune cells. Also, the cytotoxicity towards a panel of cancer cell lines and human lung fibroblast normal cell line, WI-38 cells, was explored to assure their safety. Compound 15b emerged as a hit in this study with potent broad spectrum antibacterial (MIC: 0.39-0.98 μg/mL) and antifungal (MIC: 0.49-0.98 μg/mL) activities, in addition to its ability to kill mycobacteria M. aurum inside an infected macrophage model with good therapeutic window. Moreover, compound 15b displayed promising activity towards resistant bacteria strains MRSA and VRE with MIC values equal 3.90 and 7.81 μg/mL, respectively. These results suggest compound 15b as a new therapeutic lead with good selectivity for further optimization and development.

Topics: Animals; Anti-Bacterial Agents; Antifungal Agents; Bacteria; Cell Line; Dose-Response Relationship, Drug; Drug Design; Fungi; Humans; Indoles; Macrophages; Mice; Microbial Sensitivity Tests; Molecular Structure; Phenotype; RAW 264.7 Cells; Structure-Activity Relationship; Thiazolidines

Drugs for treating Leishmaniasis, a parasitic tropical orphan disease, currently have several limitations on their use, which topical treatments could alleviate. Topical treatment requires penetration of drugs deep into the skin, which is aided by encapsulation within ultradeformable liposomes. Penetrability depends on the flexibility of the lipid membrane, which may be affected by the drugs. We have studied the biophysical effects of four anti-Leishmania drugs (miltefosine (Milt), amphotericin B (AmpB), indole (Ind), and imiquimod (Imiq)) on a soy phosphatidylcholine/sodium cholate membrane. Using diffuse X-ray scattering techniques, we determined bending modulus ( K

Topics: Amphotericin B; Antiprotozoal Agents; Imiquimod; Indoles; Liposomes; Phosphatidylcholines; Phosphorylcholine; Sodium Cholate; X-Ray Diffraction

The adequate formulation of topical vehicles to treat skin diseases is particularly complex. A desirable formulation should enhance the accumulation of the active drugs in the target tissue (the skin), while avoiding the penetration enhancement to be so large that the drugs reach the systemic circulation in toxic amounts. We have evaluated the transcutaneous penetration of three drugs chosen for their widely variable physicochemical properties: Amphotericin B, Imiquimod and Indole. We incorporated the drugs in fluid or ultra-flexible liposomes. Ultra-flexible liposomes produced enhancement of drug penetration into/through human skin in all cases in comparison with fluid liposomes without detergent, regardless of drug molecular weight. At the same time, our results indicate that liposomes can impede the transcutaneous penetration of molecules, in particular small ones.

Topics: Administration, Cutaneous; Amphotericin B; Animals; Drug Delivery Systems; Drug Stability; Humans; Imiquimod; Indoles; Liposomes; Mice; Skin Absorption

2-(Indole-3-yl)-thiochroman-4-ones were synthesized via ionic liquid and tested for in vitro antifungal activity. The contribution of ionic liquid to Michael addition reaction is significant. Structures of all compounds are elucidated by (1)H NMR, (13)C NMR and HRMS. Most of these compounds showed better antifungal activity than fluconazole. The results suggest that 2-(indole-3-yl)-thiochroman-4-ones would be efficient antifungal agents.

Topics: Antifungal Agents; Fungi; Indoles; Ionic Liquids; Molecular Structure; Structure-Activity Relationship

Three-component coupling of aldehyde, indole and kojic acid has been achieved using a catalytic amount of InCl(3) under solvent free conditions to produce a novel series of 2-substituted aryl(indolyl)kojic acid derivatives in good yields and with high selectivity. These compounds are found to exhibit potent antifungal properties.

Topics: Aldehydes; Anti-Bacterial Agents; Antifungal Agents; Catalysis; Indium; Indoles; Microbial Sensitivity Tests; Pyrones